Diffusion-weighted and dynamic contrast-enhanced MRI of pancreatic adenocarcinoma xenografts: associations with tumor differentiation and collagen content

Purpose: The aggressiveness of pancreatic ductal adenocarcinoma (PDAC) is highly dependent on the level of differentiation and the composition of the stroma. In this preclinical study, we investigated the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as noninvasive methods for providing information on the differentiation and the stroma of PDACs. Methods: Xenografted tumors initiated from four PDAC cell lines (BxPC-3, Capan-2, MIAPaCa-2, and Panc-1) were included in the study. DW-MRI and DCE-MRI were carried out on a 7.05-T MR scanner, and tumor images of ADC (the apparent diffusion coefficient), Ktrans (the volume transfer constant of Gd-DOTA), and v(e) (the fractional distribution volume of Gd-DOTA) were produced. The level of differentiation and the amount and structure of collagen I and collagen IV were determined by examining histological preparations. Results: Differentiated tumors showed lower levels of collagen I and collagen IV than non-differentiated tumors. Significant correlations were found between ADC and ve, and both parameters differentiated clearly between collagenrich non-differentiated tumors and differentiated tumors containing less collagen. Conclusion: Differentiated PDAC xenografts show higher ADC values and higher v(e) values than their non-differentiated counterparts. This observation supports the application of parametric MR images as tumor biomarkers in PDAC. Patients showing low values of ADC and v(e) most likely have non-differentiated tumors with extensive stroma and, hence, poor prognosis.